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目的研究慢性乙型肝炎病毒(HBV)感染过程中外周血T细胞表达细胞因子的调节作用。方法 60例慢性HBV感染者分为免疫耐受期组、免疫清除期组和非活动期组,20例健康人群作为对照组。另收集21例乙型肝炎病毒e抗原(HBe Ag)阳性的慢性乙型肝炎患者,进行恩替卡韦治疗6个月。全自动生化分析仪检测血清丙氨酸氨基转移酶(ALT)水平,PCR法检测HBV DNA载量,流式细胞术检测T细胞γ干扰素(IFN-γ)和白细胞介素4(IL-4)水平。结果慢性HBV感染者的外周血CD4~+T细胞和CD8~+T细胞的IFN-γ水平与HBV DNA载量呈反比,IFN-γ/IL-4比率与HBV DNA载量和血清ALT水平均呈反比。此外,从免疫耐受期到非活动病毒携带期,T细胞的IFN-γ水平逐渐增加、IL-4水平逐渐降低,且与对照组相比,免疫耐受期患者的T细胞表达IL-4增加且IFN-γ减少,到非活动携带期其细胞因子表达逐渐恢复。慢性乙型肝炎患者经恩替卡韦抗病毒治疗后,血清HBV DNA载量和ALT水平均明显降低,同时其外周血CD8~+T细胞的IFN-γ水平及IFN-γ/IL-4比率均明显增加。结论慢性HBV感染过程中,外周血T细胞的IFN-γ和IL-4发挥双向调节作用,与恩替卡韦抗病毒疗效相关。
Objective To study the regulatory effect of cytokines expressed by peripheral blood T cells during chronic hepatitis B virus (HBV) infection. Methods Sixty patients with chronic HBV infection were divided into immune tolerance group, immune clearance group and inactive group, and 20 healthy people as control group. Another 21 patients with chronic hepatitis B who were positive for hepatitis B virus e antigen (HBeAg) were enrolled and entecavir was given for 6 months. Serum alanine aminotransferase (ALT) levels were detected by automatic biochemical analyzer. HBV DNA load was detected by PCR. The levels of IFN-γ and IL-4 )Level. Results The levels of IFN-γ in CD4 ~ + T cells and CD8 ~ + T cells in peripheral blood of chronic HBV infected patients were inversely proportional to the level of HBV DNA. The IFN-γ / IL-4 ratio, HBV DNA load and serum ALT level Inversely. In addition, the level of IFN-γ in T cells gradually increased and the level of IL-4 decreased gradually from the period of immune tolerance to inactive virus. Compared with the control group, the T cells in immune-tolerant patients expressed IL-4 Increased and IFN-γ decreased, to the inactive carrying period of its cytokine expression gradually restored. Serum HBV DNA load and ALT levels were significantly decreased in patients with chronic hepatitis B after antiviral treatment with entecavir, and the levels of IFN-γ and IFN-γ / IL-4 in peripheral blood CD8 + T cells were significantly increased . Conclusion During the course of chronic HBV infection, IFN-γ and IL-4 in peripheral blood T cells play a bidirectional role in the regulation of antiviral efficacy of entecavir.